【摘要】 目的:建立心力衰竭大鼠模型,探讨心力衰竭发生发展过程与抗β1肾上腺素受体(β1AR)自身抗体产生的关系,并观察该抗体的生物学效应及其信号转导通路。方法:采用缩窄腹主动脉法制备心力衰竭大鼠模型;应用酶联免疫吸附测定(ELISA)技术,检测心力衰竭大鼠血清中的抗β1AR自身抗体;利用亲和层析法纯化心力衰竭大鼠抗体阳性血清中的IgG,观察该抗体IgG对乳鼠心肌细胞搏动频率和成年大鼠心肌细胞腺苷酸环化酶活性的影响。结果:(1)心力衰竭大鼠血清中抗β1AR自身抗体的阳性率(82.8%)和抗体滴度[1∶(67.3±2.4)]明显高于假手术组5%,[1∶(17.3±2.0)](P<0.01);(2)纯化的抗体IgG既可增加乳鼠心肌细胞的搏动频率,还可增强成鼠心肌细胞腺苷酸环化酶的活性,使cAMP产生量增加。结论:心力衰竭可以诱导大鼠血清中抗β1AR自身抗体的产生,该抗体具有激动剂样正性变时效应,可增强腺苷酸环化酶活性。提示该自身抗体可能通过β1AR-Gs-AC-cAMP-PKA信号通路对心脏产生病理损害。更多还原

【Abstract】 AIM: The present study was designed to examine the relationship between development of heart failure（HF） and the genesis of autoantibody against β₁-adrenoceptor（β₁AR） by establishing an adult rat model of HF,and explore the biological effects of the autoantibody and the signal pathway by which the anti-β₁AR-autoantibody may contribute to the pathogenesis of HF.METHODS: Male adult rats were subjected to establish HF model by constricting the abdominal aorta.The autoantibody against β₁AR from the sera of rats with HF was screened by ELISA assay.IgG in the positive sera of rats with HF was prepared by using a MabTrap Kit（Amersham） following the manufacturer’s instructions.The effects of β₁AR autoantibody on the beating rate of cultured neonatal rat cardiomyocytes and on the activity of adenylate cyclase（AC） in adult isolated cardiomyocytes were observed.RESULTS:（1） The positive rate and the titer of anti-β₁AR autoantibody in the sera of rats with HF [82.8%,1∶（67.3±2.4）] were obviously higher than those in sham group [5%,1∶（17.3±2.0）]（P<0.01）.（2） The IgG in the positive sera from the rats with HF increased the beating rate of cultured neonatal rat cardiomyocytes,and enhanced the activity of AC in adult isolated cardiomyocytes,as evidenced by the increased cyclic adenosine monophosphate（cAMP） content.CONCLUSION: Taken together,these results demonstrated that HF induced the generation of autoantibody against β₁AR in an animal model and the autoantibody possessed an ’agonistic-like’ positive chronotropic effect,enhanced the activity of AC,suggesting that the autoantibody against β₁AR may contribute to the pathogenesis of HF as an agonist through β₁AR-Gs-AC-cAMP-PKA signal pathway.更多还原